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A CRISPR/Cas9 gene editing strategy has been remarkable in excising segments of integrated HIV-1 DNA sequences from the genome of latently infected human cell lines and by introducing InDel mutations, suppressing HIV-1 replication in patient-derived CD4+ T-cells, ex vivo . Here, we employed a short version of the Cas9 endonuclease, saCas9, together with a multiplex of guide RNAs (gRNAs) for targeting the viral DNA sequences within the 5′-LTR and the Gag gene for removing critically important segments of the viral DNA in transgenic mice and rats encompassing the HIV-1 genome. Tail-vein injection of transgenic mice with a recombinant Adeno-associated virus 9 (rAAV 9 ) vector expressing saCas9 and the gRNAs, rAAV:saCas9/gRNA, resulted in the cleavage of integrated HIV-1 DNA and excision of a 978 bp DNA fragment spanning between the LTR and Gag gene in the spleen, liver, heart, lung and kidney as well as in the circulating lymphocytes. Retro-orbital inoculation of rAAV 9 :saCas9/gRNA in transgenic rats eliminated a targeted segment of viral DNA and substantially decreased the level of viral gene expression in circulating blood lymphocytes. The results from the proof-of-concept studies, for the first time, demonstrate the in vivo eradication of HIV-1 DNA by CRISPR/Cas9 on delivery by an rAAV 9 vector in a range of cells and tissues that harbor integrated copies of viral DNA.

The highly pathogenic avian influenza (HPAI) H5N1 virus that emerged in southern China in the mid-1990s has in recent years evolved into the first HPAI panzootic. In many countries where the virus was detected, the virus was successfully controlled, whereas other countries face periodic reoccurrence despite significant control efforts. A central question is to understand the factors favoring the continuing reoccurrence of the virus. The abundance of domestic ducks, in particular free-grazing ducks feeding in intensive rice cropping areas, has been identified as one such risk factor based on separate studies carried out in Thailand and Vietnam. In addition, recent extensive progress was made in the spatial prediction of rice cropping intensity obtained through satellite imagery processing. This article analyses the statistical association between the recorded HPAI H5N1 virus presence and a set of five key environmental variables comprising elevation, human population, chicken numbers, duck numbers, and rice cropping intensity for three synchronous epidemic waves in Thailand and Vietnam. A consistent pattern emerges suggesting risk to be associated with duck abundance, human population, and rice cropping intensity in contrast to a relatively low association with chicken numbers. A statistical risk model based on the second epidemic wave data in Thailand is found to maintain its predictive power when extrapolated to Vietnam, which supports its application to other countries with similar agro-ecological conditions such as Laos or Cambodia. The model's potential application to mapping HPAI H5N1 disease risk in Indonesia is discussed.

Managing complex disaster situations is a challenging task because of the large number of actors involved and the critical nature of the events themselves. In particular, the different terminologies and technical vocabularies that are being exchanged among Emergency Responders (ERs) may lead to misunderstandings. Maintaining a shared semantics for exchanged data is a major challenge. To help to overcome these issues, we elaborate a modular suite of ontologies called POLARISCO that formalizes the complex knowledge of the ERs. Such a shared vocabulary resolves inconsistent terminologies and promotes semantic interoperability among ERs. In this work, we discuss developing POLARISCO as an extension of Basic Formal Ontology (BFO) and the Common Core Ontologies (CCO). We conclude by presenting a real use-case to check the efficiency and applicability of the proposed ontology.

Land use changes in Europe contribute to the decline of once‐abundant species. While these declines are well documented for some species, other, more elusive species could quietly disappear. As a result, small mustelids are believed to be declining across their historical range. Their small size and elusive ecology make small mustelids challenging to monitor and thus remain understudied. In this study, we tested the effectiveness of three camera trap‐based methods to monitor common weasel Mustela nivalis, stoat Mustela erminea, and European polecat Mustela putorius. We deployed unenclosed, semi‐enclosed, and fully enclosed camera traps in a clustered design incorporating all methods during the fall of 2023 in two extensive agricultural areas in the Netherlands. Using a multi‐scale occupancy approach, we assessed (1) how detection probabilities differ among the three camera trap methods for each small mustelid species and (2) how scent‐based lures and placement near passages influenced detection probabilities. We found that weasels had the highest detection probability in fully enclosed camera traps placed within clusters containing a scent‐based lure. The detection probability of stoats was highest in fully enclosed camera traps, regardless of the presence or absence of lure, as well as in unenclosed camera traps with no lure nearby. Polecats had the highest detection probability in unenclosed camera traps, regardless of lure presence, and in semi‐enclosed camera traps without lure nearby. Placing camera traps near passages increased detection probability for all three species. Practical implication: This study advances monitoring protocols for small mustelids, a group facing suspected population declines despite limited data. We highlight different detection probabilities among three mustelid species using various camera‐trap methods. Camera trap placement and species‐specific use of scent‐based lures, beneficial for weasels but not for stoats or polecats, should be considered by researchers and wildlife managers. Combining fully enclosed and unenclosed camera traps enhances species detection and offers broader ecological insights by monitoring other prey and predator mammals as bycatch. Our findings provide practical guidance for large‐scale monitoring efforts of small mustelids across Europe. Samenvatting Veranderingen in landgebruik in Europa dragen bij aan de afname van soorten die ooit veel voorkwamen. Hoewel deze afnames voor sommige soorten goed vastgelegd zijn, kunnen andere, meer ongrijpbare soorten stilzwijgend uit het landschap verdwijnen. Kleine marterachtigen nemen daardoor vermoedelijk af in hun historische verspreidingsgebied. Hun kleine lichaamsbouw en schuwe leefwijze maken het lastig om kleine marterachtigen te monitoren, waardoor ze weinig bestudeerd zijn. In dit onderzoek hebben wij de effectiviteit getest van drie cameravalmethoden om de wezel Mustela nivalis, hermelijn Mustela erminea en bunzing Mustela putorius te monitoren. In de herfst van 2023 hebben we in twee extensieve landbouwgebieden standaard, semi‐ en volledig gesloten cameravallen geplaatst in een clusteropzet waarin alle methoden vergeleken werden. Met een multi‐scale occupancy‐model onderzochten we (1) hoe detectiekansen per soort verschillen tussen de drie cameravalmethoden en (2) hoe geurlokstoffen en plaatsing bij doorgangen de detectiekans beïnvloeden. We vonden dat wezels de hoogste detectiekans hadden in volledig gesloten cameravallen die binnen clusters waren geplaatst met een lokstof. Hermelijnen hadden de hoogste detectiekans in volledig gesloten cameravallen, onafhankelijk van de aanwezigheid van een lokstof, en ook bij standaard cameravallen zonder lokstof. Bunzingen hadden de hoogste detectiekans in standaard cameravallen, ongeacht lokstof, en in semi‐gesloten cameravallen zonder lokstof. Het plaatsen van cameravallen bij doorgangen verhoogde de detectiekans voor alle drie de soorten. Praktische implicatie: Dit onderzoek levert een bijdrage aan monitoringsprotocollen voor kleine marterachtigen, een groep waarvan populatieafnames worden vermoed ondanks beperkte gegevens. We tonen aan dat de detectiekans per soort verschilt tussen cameravalmethoden. Tijdens het monitoren dient rekening gehouden te worden met cameraval plaatsing bij doorgangen en soortspecifiek gebruik van geurlokstoffen, die nuttig zijn voor wezels maar niet voor hermelijnen en bunzingen. Het combineren van gesloten en standaard cameravallen verhoogt de kans op detectie en biedt bredere ecologische inzichten doordat ook andere predator‐ en prooidieren als bijvangst worden gemonitord. Onze resultaten bieden praktische handvatten voor grootschalige monitoring van kleine marterachtigen in Europa. Small mustelids like weasels, stoats and polecats are suspected to be declining in Europe but are difficult to monitor. This study tested three camera trap designs, with and without scent‐based lures, in the Netherlands to compare detection probabilities for each species. Results show that detection success varies by species, trap type, lure use and placement, providing practical guidance for large‐scale monitoring and conservation efforts.

Glutamine commonly becomes a conditionally essential amino acid in cancer. Glutamine is supplied to the cell by transporters such as ASCT2 (SLC1A5), which is frequently upregulated in multiple cancers. Here we investigated the expression of ASCT2 in endometrial carcinoma, and evaluated the contribution of ASCT2 to glutamine uptake and endometrial cancer cell growth. Analysis of human gene expression data showed that ASCT2 was significantly upregulated in both endometrioid and serous subtypes of endometrial carcinoma, compared to normal, age-matched endometrium. Furthermore, immunohistochemical staining of primary human endometrioid adenocarcinomas showed that tumours stain positive for ASCT2 in either a uniform or mosaic expression pattern, while normal adjacent glands appeared predominantly negative for ASCT2 staining. Chemical inhibition of glutamine transport by benzylserine or GPNA led to a significant decrease in endometrial cancer cell growth and spheroid cross-sectional area. ASCT2 knockdown recapitulated the decrease of cell growth and spheroid cross-sectional area in HEC1A cells, suggesting a reliance on ASCT2-mediated glutamine uptake. ASCT2 knockdown in Ishikawa cells led to lower glutamine uptake and cell growth, but did not affect spheroid area. Ishikawa cells express higher levels of the glutamine transporter SNAT1 compared to HEC1A cells, suggesting these cells may rely on both ASCT2 and SNAT1 for glutamine uptake. Since SNAT1 is also significantly upregulated in the endometrioid and serous subtypes, these data indicate that ASCT2 and SNAT1 could be used as markers of malignancy, and/or potential therapeutic targets in patients with endometrial carcinoma.

BackgroundThe shift from routine antibiotics towards omitting antibiotics for uncomplicated acute diverticulitis opens up the possibility for outpatient instead of inpatient treatment, potentially reducing the burden of one of the most common gastrointestinal diseases in the Western world.PurposeAssessing the safety and cost savings of outpatient treatment in acute colonic diverticulitis.MethodsPubMed and EMBASE were searched for studies on outpatient treatment of colonic diverticulitis, confirmed with computed tomography or ultrasound. Outcomes were readmission rate, need for emergency surgery or percutaneous abscess drainage, and healthcare costs.ResultsA total of 19 studies with 2303 outpatient treated patients were included. These studies predominantly excluded patients with comorbidity or immunosuppression, inability to tolerate oral intake, or lack of an adequate social network. The pooled incidence rate of readmission for outpatient treatment was 7% (95%CI 6–9%, I2 48%). Only 0.2% (2/1288) of patients underwent emergency surgery, and 0.2% (2/1082) of patients underwent percutaneous abscess drainage. Only two studies compared readmission rates outpatients that had similar characteristics as a control group of inpatients; 4.5% (3/66) and 6.3% (2/32) readmissions in outpatient groups versus 6.1% (4/66) and 0.0% (0/44) readmissions in inpatient groups (p = 0.619 and p = 0.174, respectively). Average healthcare cost savings for outpatient compared with inpatient treatment ranged between 42 and 82%.ConclusionOutpatient treatment of uncomplicated diverticulitis resulted in low readmission rates and very low rates of complications. Furthermore, healthcare cost savings were substantial. Therefore, outpatient treatment of uncomplicated diverticulitis seems to be a safe option for most patients.

A recent study has suggested that the brain-expressed genes for G72 and D -amino-acid oxidase (DAAO) exert an influence on susceptibility to schizophrenia. Our aim was to replicate this finding in German schizophrenic patients and to assess whether G72 and DAAO might also contribute to the development of bipolar affective disorder. We genotyped seven single-nucleotide polymorphisms (SNPs) in the G72 gene and three in the DAAO gene in 599 patients (299 schizophrenic, 300 bipolar) and 300 controls. At G72, individual SNPs and a four-marker haplotype were associated with schizophrenia. The most significant SNP as well as the haplotype were also associated with bipolar affective disorder (BPAD). DAAO was associated with schizophrenia, but not with BPAD. The association of variation at G72 with schizophrenia as well as BPAD provides molecular support for the hypothesis that these two major psychiatric disorders share some of their etiologic background.

An important question in regional climate downscaling is whether to constrain (nudge) the interior of the limited-area domain toward the larger-scale driving fields. Prior research has demonstrated that interior nudging can increase the skill of regional climate predictions originating from historical data. However, there is concern that nudging may also inhibit the regional model’s ability to properly develop and simulate mesoscale features, which may reduce the value added from downscaling by altering the representation of local climate extremes. Extreme climate events can result in large economic losses and human casualties, and regional climate downscaling is one method for projecting how climate change scenarios will affect extreme events locally. In this study, the effects of interior nudging are explored on the downscaled simulation of temperature and precipitation extremes. Multidecadal, continuous Weather Research and Forecasting model simulations of the contiguous United States are performed using coarse reanalysis fields as proxies for global climate model fields. The results demonstrate that applying interior nudging improves the accuracy of simulated monthly means, variability, and extremes over the multidecadal period. The results in this case indicate that interior nudging does not inappropriately squelch the prediction of temperature and precipitation extremes and is essential for simulating extreme events that are faithful in space and time to the driving large-scale fields.

This study evaluates interior nudging techniques using the Weather Research and Forecasting (WRF) model for regional climate modeling over the conterminous United States (CONUS) using a two-way nested configuration. NCEP–Department of Energy Atmospheric Model Intercomparison Project (AMIP-II) Reanalysis (R-2) data are downscaled to 36 km × 36 km by nudging only at the lateral boundaries, using gridpoint (i.e., analysis) nudging and using spectral nudging. Seven annual simulations are conducted and evaluated for 1988 by comparing 2-m temperature, precipitation, 500-hPa geopotential height, and 850-hPa meridional wind to the 32-km North American Regional Reanalysis (NARR). Using interior nudging reduces the mean biases for those fields throughout the CONUS compared to the simulation without interior nudging. The predictions of 2-m temperature and fields aloft behave similarly when either analysis or spectral nudging is used. For precipitation, however, analysis nudging generates monthly precipitation totals, and intensity and frequency of precipitation that are closer to observed fields than spectral nudging. The spectrum of 250-hPa zonal winds simulated by the WRF model is also compared to that of the R-2 and NARR. The spatial variability in the WRF model is reduced by using either form of interior nudging, and analysis nudging suppresses that variability more strongly than spectral nudging. Reducing the nudging strengths on the inner domain increases the variability but generates larger biases. The results support the use of interior nudging on both domains of a two-way nest to reduce error when the inner nest is not otherwise dominated by the lateral boundary forcing. Nevertheless, additional research is required to optimize the balance between accuracy and variability in choosing a nudging strategy.